Biology subjects

Gonzalez, V.

Publications and source records attributed to Gonzalez, V..

17 recordsLinked to original sources

bioRxiv2026

An implantable sensor network for large-scale cellular force mapping in living embryos

Mechanical forces generated by cells are fundamental regulators of embryonic development, yet how locally generated forces are integrated across tissues to drive large-scale morphogenesis remains poorly understood. Addressing this question requires direct quantitative mapping of intercellular forces across tissue scale with cellular resolution while preserving native tissue architectures and dynamics, a capability not yet achieved. Here, we introduce FORCENET, an implantable force-sensing network that enables quantitative tissue-scale force mapping at cellular resolution within living embryos. FORCENET consists of a microfabricated network of ultrathin elastic sensors whose three-dimensional deformations are tracked over time and converted into intercellular force maps through physics-based reconstruction. FORCENET covers hundreds of cells while occupying a total volume 6- to 20-fold smaller than that of a single cell. Anatomical measurements, three-dimensional fluorescent imaging, and cell density and speed tracking confirmed that FORCENET seamlessly integrates within developing embryos without perturbing cell motion and proliferation, tissue architecture, and embryonic development. Applied to zebrafish gastrulation, FORCENET revealed that intercellular forces are dynamically coordinated across supracellular length scales of ~30-210 m. Inhibition of fibroblast growth factor signaling accelerated force accumulation and shortened the force-coordination length scales despite only modest changes in cell density and kinematics, demonstrating that FORCENET uncovers information not readily inferred from cell tracking alone. FORCENET establishes a scalable platform for in vivo force mapping and reveals that cell-generated forces are coordinated into supracellular mechanical patterns that are regulated by developmental signaling.

developmental biology↗

bioRxiv2026

Effects of spectral light quality on growth, photosynthetic pigments and bioactive compounds in Brassicaceae microgreens

LED spectral composition is an important tool for improving the growth and nutritional quality of microgreens cultivated in controlled environments. This study evaluated the effects of three LED light treatments on growth, morphology, pigments, primary metabolites, phenolic composition, and antioxidant capacity in arugula (Eruca sativa), mustard (Brassica juncea), and radish (Raphanus sativus) microgreens. Microgreens were cultivated under controlled environmental conditions and exposed to broad-spectrum white (W), blue-enriched white (WB), and red-enriched white (R) light at a photosynthetic photon flux density of 200 micromol/m2/s. Light quality did not affect yield in any species. However, R increased cotyledon area in arugula by 50 to 60% and promoted hypocotyl elongation in both arugula and radish, whereas W resulted in the longest hypocotyls in mustard. Photosynthetic pigment composition responded differently among species. In mustard, WB increased the chlorophyll a/b ratio (1.12 to 1.18), whereas lutein concentration decreased from 7.06 to 4.20 mg 100 g/FW. Primary metabolism also responded to light treatments in a species-dependent manner. In mustard, W increased glucose (0.43 vs. 0.26 and 0.29 g 100 g/ FW) and fructose (0.33 vs. 0.20 and 0.22 g 100 g/ FW) concentrations compared with WB and R. Organic acid composition was more responsive to light treatments in radish, with higher concentrations under R. Phenolic metabolism also responded in a species-dependent manner. In mustard, W increased total phenolic content to 0.25 mg GAE g/FW compared with 0.15 mg GAE g/FW under WB and R, and ABTS antioxidant capacity to 1.17 mg TE g/FW compared with 0.74 and 0.75 mg TE g/FW under WB and R, respectively. Individual phenolic compounds were also affected by light treatments, particularly in arugula and mustard. These findings demonstrate that the effects of LED spectral composition on microgreen quality are highly species-dependent. Therefore, LED light spectra should be optimized according to the target species and the desired quality attributes rather than applying a single lighting strategy to all Brassicaceae microgreens.

plant biology↗

bioRxiv2026

Polarization-engineered aberration-resilient light sheet microscopy

Light sheet fluorescence microscopy enables volumetric imaging with high imaging speed, optical sectioning capability, and reduced photobleaching and phototoxicity, and has become a workhorse in bioimaging. However, widely adopted Gaussian light sheets face an inherent trade-off between axial resolution and field-of-view due to diffraction. State-of-the-art nondiffracting light sheets--including Bessel beam, Airy beam, and lattice light sheet--alleviate this trade-off but suffer from optical aberrations that compromise performance with increasing imaging depth. While the integration of adaptive optics offers a promising solution, such integrated systems are typically complex, expensive, and slow due to the need for serial mapping and correction of spatially varying aberrations across the specimen. Here, we present polarization-engineered aberration-resilient light sheet (PEARLS), a new class of monochromatic nondiffracting light sheet with temporally invariant profile and robustness to optical aberrations. In comparison with existing light sheets, PEARLS showed significantly reduced photobleaching and enhanced aberration-resilience, permitting imaging of three-dimensional subcellular dynamics in optically complex environments. We applied PEARLS for noninvasive observations of biological dynamics in various living systems, revealing phenotypic diversity across spatial and temporal scales--from rapid membrane dynamics and organelle interactions in cultured cells to coordinated mitosis and cell migrations in developing embryos.

cell biology↗

bioRxiv2026

Compatibility and Multi-Season Field Evaluation of Trichoderma koningiopsis Integrated with Fungicides for Soybean Charcoal Rot Management

Soybean (Glycine max [L.] Merr.) productivity is frequently compromised by soil-borne pathogens. Macrophomina phaseolina (Mp), the causal agent of charcoal rot, can produce important soybean yield losses especially when hot and dry weather prevails. Integrating biological control agents with chemical seed treatments represents a promising strategy for improving disease management. This study aimed to (i) assess the in vitro compatibility of Trichoderma koningiopsis with commercial fungicide seed treatments, and (ii) evaluate the field performance of T. koningiopsis, alone or combined with compatible fungicides, across three soybean growing seasons. Compatibility assays revealed fungicide-specific effects, with Acronis(R) classified as non-fungitoxic and Topseed Extra as moderately fungitoxic. Across field seasons, Mp inoculation reduced seedling emergence, while several seed treatments improved emergence compared to the inoculated control, however, treatment effects varied markedly among years. Disease severity did not differ significantly among treatments in any season, and yield responses were strongly modified by environmental conditions rather than treatment effects. Temperature-response assays showed that T. koningiopsis exhibited optimal growth between 28 to 30{degrees}C and complete inhibition above 40{degrees}C, indicating high thermal sensitivity. The results demonstrate that T. koningiopsis can be integrated with compatible fungicides and may enhance early stand establishment under favorable conditions, but its field performance is strongly limited by high temperatures. These findings highlight the importance of environmental conditions when biological seed treatments are used.

plant biology↗

bioRxiv2025

Prophage and SaPI diversity in local clinical Staphylococcus aureus reveal hidden drivers of virulence.

Prophages are key drivers of bacterial evolution, genomic variability, virulence, and ecological adaptation. Here, we examined the prophage diversity of 109 Staphylococcus aureus clinical isolates from four tertiary care hospitals in Mexico City, integrating comparative analyses with 993 international genomes. Prophages were detected in 97% of the local strains, mirroring the near-ubiquitous presence (99%) observed globally. We identified 216 genomic regions encoding putative prophage functional elements. Using Mitomycin C induction, we recovered 17 temperate phages, 12 of which were functionally active and capable of lysogeny-lysis switching and reinfection. Induced phages lacked virulence or antibiotic resistance genes, in contrast to 55% of the predicted prophages in local S. aureus isolates that harbored known virulence factors. Moreover, 19% of the predicted prophages were phage-inducible chromosomal islands (PICIs) related to SaPI1, SaPI2, and SaPIpt1028. These PICIs encode anti-phage defense systems (63%) and virulence genes (27%), such as tsst-1 and hlb. Our findings reveal a complex prophage and PICI landscape in S. aureus circulating in Mexican hospitals, with implications for phage- host dynamics, horizontal gene transfer, and the evolution of pathogenic potential across geographically diverse populations. ImportanceStaphylococcus aureus is a major hospital pathogen whose evolution is driven by mobile genetic elements including prophages and phage-inducible chromosomal islands (PICIs). Although computational analyses predict prophages in nearly all S. aureus genomes, we demonstrate that only a small fraction is functionally active. Through experimental induction of clinical isolates from Mexican hospitals, we recovered active prophages that surprisingly lacked virulence genes, in contrast to the predicted prophages that frequently harbor virulence factors. Importantly, we discovered that many predicted "prophages" are PICIs carrying anti-phage defenses and toxins. These findings challenge the current prophage prediction methods and reveal the complex prophage-PICI landscape that shapes horizontal gene transfer and pathogenic evolution in clinical S. aureus populations.

microbiology↗

bioRxiv2025

Hyper-responsiveness of cancer stem cells to microenvironmental cues controls metastasis and therapy response through YAP/TAZ/TEAD

Cancer stem cells (CSCs) are key drivers of metastasis and therapy resistance but have been challenging to visualize and study in situ. Using a fluorescent CSC reporter, we observed very different population dynamics for CSCs and nonCSCs during metastatic lung colonization in breast cancer models. CSC expansive self-renewal drives early lesion formation before switching to a maintenance mode of balanced self-renewal and differentiation, whereupon nonCSC proliferation takes over as the main driver of metastatic expansion. Mechanistic analyses showed that CSCs are hyper-responsive to microenvironmental cues such as cell crowding and nutrient availability, suggesting a novel role for CSCs as sensors and early responders to fluctuating local conditions in the tumor. Incoming signals converge on YAP/TAZ/TEAD, with heightened CSC sensitivity and response supported by elevated receptor expression and increased chromatin accessibility around enhancers with TEAD binding sites. Targeting inputs to the YAP/TAZ/TEAD node reversed chemotherapy-induced enrichment of CSCs in lung metastases. HighlightsO_LIDifferent population dynamics for breast cancer stem cells (CSCs) and their differentiated progeny in early metastatic colonization C_LIO_LICSCs are hyper-responsive to microenvironmental cues and serve as sensors of local conditions for the tumor C_LIO_LIMany microenvironmental inputs converge on YAP/TAZ to regulate self-renewal vs differentiation fate decisions in the CSC C_LIO_LITargeting YAP/TAZ input pathways blocks chemotherapy-induced enrichment of CSCs C_LI

cancer biology↗

bioRxiv2024

Viral susceptibility and innate immune competency of Carollia perspicillata bat cells produced for virological studies

Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Sebas short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using a pseudotyped virus library and authentic virus infections, we show that these C. perspicillata cell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with VSV and MERS-CoV induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and these C. perspicillata cell lines will enable studies on virus-host interactions in bats.

microbiology↗

bioRxiv2024

Disrupted developmental signaling induces novel transcriptional states

Signaling pathways induce stereotyped transcriptional changes as stem cells progress into mature cell types during embryogenesis. Signaling perturbations are necessary to discover which genes are responsive or insensitive to pathway activity. However, gene regulation is additionally dependent on cell state-specific factors like chromatin modifications or transcription factor binding. Thus, transcriptional profiles need to be assayed in single cells to identify potentially multiple, distinct perturbation responses among heterogeneous cell states in an embryo. In perturbation studies, comparing heterogeneous transcriptional states among experimental conditions often requires samples to be collected over multiple independent experiments. Datasets produced in such complex experimental designs can be confounded by batch effects. We present Design-Aware Integration of Single Cell ExpEriments (DAISEE), a new algorithm that models perturbation responses in single-cell datasets with a complex experimental design. We demonstrate that DAISEE improves upon a previously available integrative non-negative matrix factorization framework, more efficiently separating perturbation responses from confounding variation. We use DAISEE to integrate newly collected single-cell RNA-sequencing datasets from 5-hour old zebrafish embryos expressing optimized photoswitchable MEK (psMEK), which globally activates the extracellular signal-regulated kinase (ERK), a signaling molecule involved in many cell specification events. psMEK drives some cells that are normally not exposed to ERK signals towards other wild type states and induces novel states expressing a mixture of transcriptional programs, including precociously activated endothelial genes. ERK signaling is therefore capable of introducing profoundly new gene expression states in developing embryos. Significance StatementSignaling perturbations produce heterogeneous transcriptional responses that must be measured at the single-cell level. Data integration techniques allow us to model these responses which, however, can be confounded by batch effects. We present a computational tool (DAISEE) for extracting the common and perturbation-specific features of single-cell datasets representing multiple experimental conditions while achieving efficient batch effect correction. DAISEE outperforms its predecessor and will enable accurate analysis of a broad range of single-cell datasets. DAISEE applied to new single-cell RNA sequencing data from zebrafish embryos shows that gain-of-function signaling perturbations can induce novel states. Our analysis suggests that a wild type endothelial cell-specification program can be activated in abnormal developmental contexts when the extracellular signal-regulated kinase (ERK) pathway is deregulated.

developmental biology↗

bioRxiv2024

Long-read sequencing and genome assembly of natural history collection samples and challenging specimens

Museum collections harbor millions of samples, largely unutilized for long-read sequencing. Here, we use ethanol-preserved samples containing kilobase-sized DNA to show that amplification-free protocols can yield contiguous genome assemblies. Additionally, using a modified amplification-based protocol, employing an alternative polymerase to overcome PCR bias, we assembled the 3.1 Gb maned sloth genome, surpassing the previous 500 Mb protocol size limit. Our protocol also improves assemblies of other difficult-to-sequence molluscs and arthropods, including millimeter-sized organisms. By highlighting collections as valuable sample resources and facilitating genome assembly of tiny and challenging organisms, our study advances efforts to obtain reference genomes of all eukaryotes.

genomics↗

bioRxiv2024

Cooperation between Nodal and FGF signals regulates zebrafish cardiac cell migration and heart morphogenesis

Asymmetric development of the vertebrate heart is driven by a complex sequence of morphogenetic cell movements, coordinated through precise interpretation of signaling cues by the heart primordia. Here, we show that Nodal signaling functions synergistically with FGF to stimulate the migration of cardiac progenitor cells (CPCs) during cardiac jogging--the first morphological asymmetry observed in zebrafish heart development. While Nodal directs the asymmetric migration of CPCs, we find FGF signaling to be dispensable for this asymmetry, suggesting that FGF plays a permissive rather than instructive role. We further demonstrate that Nodal signaling induces asymmetries in actin cytoskeletal dynamics that correlate with the directional migration of CPCs, while FGF does not influence this actin asymmetry. In addition to influencing jogging, FGF and Nodal synergize to ensure proper heart looping. We also provide evidence that FGF contributes to heart looping by promoting the differentiation of the second heart field. Together, these findings offer insight into how the spatiotemporal dynamics of signaling pathways regulate the cellular behaviors driving organ morphogenesis. Summary statementThis study explores the synergistic and independent roles of Nodal and FGF signaling in generating heart asymmetry.

developmental biology↗

bioRxiv2023

The elite common bean Phaseolus vulgaris cultivar Pinto Saltillo hosts a rich and diverse array of plant-growth promoting bacteria in its rhizosphere.

The rhizosphere of crop plants is a nutrient-rich niche that is inhabited by many microorganisms. Root-associated microorganisms play a crucial role in crop yields in agriculture. Given the ample diversity of varieties and cultivars of the common bean (Phaseolus vulgaris) used in agriculture, it is important to characterize their bacterial communities. In this study, we analyzed the bacterial rhizosphere components of the bean cultivar Pinto Saltillo, which is widely produced and consumed in Mexico. Bulk soil and rhizosphere samples from the P. vulgaris cultivar Pinto Saltillo were collected in situ from plots with and without cultivation history. Metagenomic analysis revealed that in both plots, the bacterial diversity in the bulk soil exceeded that in the rhizosphere. Moreover, diversity and taxonomic composition analysis confirmed the dominance of Proteobacteria in the rhizosphere. Comparisons with pairs of bulk soil-rhizosphere metagenomes of other cultivated plants (maize, wheat, tomato, cucumber, and the model plant Arabidopsis) indicated a pronounced rhizosphere effect of the cultivar Pinto Saltillo, particularly regarding the presence of bacterial genera already known as plant growth promoters, including Rhizobium. Metagenome-assembled genomes (MAGs) reconstructed from metagenomes confirmed a diverse set of species at the OTU level, closely related to this group of microorganisms. Our analysis underscores the association of R. sophoriradicis strains as the primary nodulating agent of common beans in the sampled agricultural fields. These findings imply that the success of common bean crops relies on microbial species that are still inadequately characterized beyond the established role of nitrogen-fixing bacteria. ImportanceSustainable agriculture is a long-term goal aimed at mitigating the impact of modern intensive and polluting agricultural technologies. Significant efforts are underway to understand the contributions of microorganisms to the health and productivity of crop plants. The common bean (Phaseolus vulgaris) is a domesticated leguminous plant native to Mesoamerica, that whose seeds provide sustenance for millions of people in America and Africa. Previous studies have illuminated the bacterial diversity of the rhizosphere microbiome in relation to plant resistance to pathogens and in the domestication process. These findings underscore the importance of investigating the bacterial rhizosphere communities in successful cultivars of the common bean. In this study, we demonstrate that the common bean cultivar Pinto Saltillo hosts a diverse array of plant-growth promoting bacteria in its rhizosphere. These findings suggest that the agricultural success of common bean cultivars could be attributed to the interplay between the plant and its rhizosphere bacterial community, rather than solely relying on nitrogen-fixing symbiosis.

microbiology↗

bioRxiv2022

Engineering a Vaccine Platform using Rotavirus A to Express SARS-CoV-2 Spike Epitopes

Human rotavirus (RV) vaccines used worldwide have been developed using live attenuated platforms. The recent development of a reverse genetics system for RVs has delivered the possibility of engineering chimeric viruses expressing heterologous peptides from other virus species to generate polyvalent vaccines. We tested the feasibility of this using two approaches. Firstly, we inserted short SARS-CoV-2 spike peptides into the hypervariable region of the simian SA11 RV strain viral protein (VP) 4. Secondly, we fused the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, or the shorter receptor binding motif (RBM) nested within the RBD, to the C-terminus of non-structural protein (NSP) 3 of the bovine RF strain RV, with or without an intervening T2A peptide. Mutating the hypervariable region of SA11 VP4 impeded viral replication, and for these mutants no cross-reactivity with spike antibodies was detected. To rescue NSP3 mutants, we established a plasmid-based reverse genetics system for the bovine RF strain. Except for the RBD mutant, all NSP3 mutants delivered endpoint titres and replication kinetics comparable to that of the WT virus. In ELISAs, cell lysates of an NSP3 mutant expressing the RBD peptide showed cross reactivity with a SARS-CoV-2 RBD antibody. 3D bovine gut enteroids were susceptible to infection by all NSP3 mutants but only RBM mutant showed cross reactivity with SARS-CoV-2 RBD antibody. The tolerability of large peptide insertions in the NSP3 segment highlights the potential for this approach in the development of vaccine vectors targeting multiple enteric pathogens simultaneously. IMPORTANCEWe explored the use of rotaviruses (RVs) to express heterologous peptides, using SARS-CoV-2 as an exemplar. Small SARS-CoV-2 peptide insertion (<34 amino acids) into the hypervariable region of the viral protein 4 (VP4) of RV SA11 strain resulted in reduced viral titre and replication, thus limiting its use as a potential vaccine expression platform. To test RF strain for its tolerance for peptide insertions, we constructed a reverse genetics system. NSP3 was C-terminally tagged with SARS-CoV-2 spike peptides of up to 193 amino acids. With a T2A-separated 193 amino acid tag on NSP3, there was little effect on the viral rescue efficiency, titre and replication. Tagged NSP3 elicited cross-reactivity with SARS-CoV-2 spike antibodies in ELISA. This is the first report describing epitope tagging of VP4, and of a reverse genetics system for the RF strain. We highlight the potential for development of RV vaccine vectors targeting multiple enteric pathogens simultaneously.

microbiology↗

bioRxiv2022

Arctic evergreening - encroaching allelopathy in a management blind spot

O_LIOngoing Arctic greening can increase productivity and reindeer pasture quality in the tundra. However, greening may also entail proliferation of unpalatable species, with distinct consequences for pastoral socio-ecological systems (SES). C_LIO_LIWe show extensive greening across 20 reindeer districts in northern Norway between 2003 and 2020. The allelopathic, evergreen dwarf-shrub crowberry biomass increased by 60%, contrasted by smaller increases of deciduous dwarf-shrubs and stagnating forb and graminoid biomass. C_LIO_LIWe found evidence, although uncertain, of a negative relationship between biomass and reindeer densities, but only among forbs, the least abundant plant group. C_LIO_LIOur results challenge the management decision-making, which aims at sustainable pasture management, but which assumes stationary density-dependent relationships. Changes in temporal vs. spatial relationships should be included as management criteria, to avoid mismanaging a SES in transition. C_LIO_LILarge-scale shift towards increased allelopathy may undermine the resource base of a key Arctic herbivore and pastoral SES. C_LI

ecology↗

bioRxiv2021

Systemic influences of mammary cancer on monocytes in mice

There is a growing body of evidence that cancer causes systemic changes. These influences are most evident in the bone marrow and blood, particularly the myeloid compartment. Here we show using mouse models of breast cancer caused by the mammary epithelial expression of the Polyoma middle T antigen that there is an increase in the number of circulating and splenic monocytes. In the circulation, cancer does not affect ratios of classical to non-classical populations monocytes nor their halflives. Single cell RNA sequencing also indicates that cancer does not induce any new monocyte populations. In the bone marrow cancer does not change monocytic progenitor number is unaffected but the proliferation rate of monocytes is higher thus providing an explanation for expansion in the circulating number. Deep RNA sequencing of these monocytic populations reveals cancer causes changes in the classical monocyte compartment with changes evident in bone marrow monocytes but more in the blood suggesting influences in both compartments. Down regulation of interferon type 1 signalling and antigen presentation were the most prominent. Consistent with this analysis down regulated genes are enriched with STAT1/STAT2 binding sites in their promoter, transcription factors required for type 1 interferon signalling. However, these transcriptome changes in mice did not replicate those found in patients with breast cancer. Consequently, mouse models of cancer may be insufficient to study the systemic influences of human cancer.

cancer biology↗

bioRxiv2021

Aire-dependent transcripts escape H3K36me3 and Raver2 induced alternative splicing to sustain central immune tolerance

Aire allows medullary thymic epithelial cells (mTECs) to express and present a large number of self-antigens for central tolerance. Although mTECs express a high diversity of self-antigen splice isoforms, the extent and regulation of alternative splicing events (ASEs) included in their transcripts, notably in those induced by Aire, is unknown. Unexpectedly, and in contrast to Aire-neutral genes, we found that the Aire-sensitive genes exhibit in Aire-positive and negative mTECs, a weak inclusion of ASEs, with about a quarter present in peripheral tissues being excluded from the thymus. We identified Raver2, as a splicing-related factor overrepresented in mTECs and dependent on H3K36me3 marks. We discovered that both Raver2 and methylation of H3K36 promoted ASE inclusion for Aire-neutral genes, leaving Aire-sensitive genes unaffected. Profiling of H3K36me3 revealed its depletion at Aire-sensitive genes, supporting a mechanism, whose setup precedes Aires expression and by which Aire-sensitive genes exhibit weak ASE inclusion through the escape of Raver2s effect. Lack of ASEs in Aire-induced transcripts highlights a role for regulatory T cells in controlling the incomplete Aire-dependent negative selection.

immunology↗

bioRxiv2020

Spatial patterns in phage-Rhizobium coevolutionary interactions across regions of common bean domestication

Bacteriophages play significant roles in the composition, diversity, and evolution of bacterial communities. Despite their importance, it remains unclear how phage diversity and phage-host interactions are spatially structured. Local adaptation may play a key role. Nitrogen-fixing symbiotic bacteria, known as rhizobia, have been shown to locally adapt to domesticated common bean at its Mesoamerican and Andean sites of origin. This may affect phage-rhizobium interactions. However, knowledge about the diversity and coevolution of phages with their respective Rhizobium populations is lacking. Here, through the study of four phage-Rhizobium communities in Mexico and Argentina, we show that both phage and host diversity is spatially structured. Cross-infection experiments demonstrated that phage infection rates were higher overall in sympatric rhizobia than in allopatric rhizobia except for one Argentinean community, indicating phage local adaptation and host maladaptation. Phage-host interactions were shaped by the genetic identity and geographic origin of both the phage and the host. The phages ranged from specialists to generalists, revealing a nested network of interactions. Our results suggest a key role of local adaptation to resident host bacterial communities in shaping the phage genetic and phenotypic composition, following a similar spatial pattern of diversity and coevolution to that in the host.

microbiology↗

bioRxiv2017

Vast population genetic diversity underlies the treatment dynamics of ETV6-RUNX1 ALL

Ensemble-averaged genome profiling of diagnostic samples suggests that acute leukemias harbor few somatic genetic alterations. We used single-cell exome and error-corrected sequencing to survey the genetic diversity underlying ETV6-RUNX1 acute lymphoblastic leukemia (ALL) at high resolution. The survey uncovered a vast range of low-frequency genetic variants that were undetected in conventional bulk assays, including additional clone-specific \"driver\" RAS mutations. Single-cell exome sequencing revealed APOBEC mutagenesis to be important in disease initiation but not in progression and identified many more mutations per cell than previously found. Using this data, we created a branching model of ETV6-RUNX1 ALL development that recapitulates the genetic features of patients. Exposure of leukemic populations to chemotherapy selected for specific clones in a dose-dependent manner. Together, these data have important implications for understanding the development and treatment response of childhood leukemia, and they provide a framework for using population genetics to deeply interrogate cancer clonal evolution.\n\nOne-Sentence SummaryAPOBEC and replication-associated mutagenesis contribute to the development of ETV6-RUNX1 ALL, creating massive leukemic population genetic diversity that results in clonal differences in susceptibilities to chemotherapy.

cancer biology↗